Monoterpenes are the smallest (C10) members of the isoprenoid family of compounds and they provide excellent model systems for studying the metabolism of complex higher terpenoids. Two types of bicyclic monoterpene cyclases (and their enantiomer synthesizing counterparts) have been selected as models for intensive study in order to provide information on the poorly understood process of allylic pyrophosphate cyclization; a reaction type of major importance in enzymatic C-C bond formation and a key step in the biosynthesis of numerous terpenoid natural products of pharmacological significance such as cannabinoids, antitumoral sesquiterpene lactones, tumor promoting phorbol esters and a wide range of antibiotics and toxins. These enzymes, designated geranyl pyrophosphate:bornyl pyrophoshate cyclase and geranyl pyrophosphate:pinene cyclase, respectively, will be purified to homogeneity and a variety of experimental approaches, including studies with substrate analogs and specifically labeled substrates, kinetic methods, binding studies and protein modification, will be used to probe the enzymology, mechanism and stereochemistry of the reactions. These comparative studies on the cyclization of geranyl pyrophosphate to the different model skeletal isomers and derivatives should provide new information on each step of the reaction from initiation to termination, and allow the construction of a general scheme for the enzymatic cyclization of allylic pyrophosphates to isoprenoid compounds.